The proposed research is concerned with the initiating events of chemical carcinogenesis. Major emphasis will be on the interaction of carcinogens with DNA and the consequence (damage and repair) of this reaction as it relates to the integrity of the cell. Damage and repair will be studied with alkaline sucrose gradients, BND-cellulose, and determination of the alkylated products. A single initiating dose of carcinogens such as methylnitrosourea will be used to examine damage and repair. The effect of carcinogens on DNA synthesis (repair and replication) and loss of alkylated products, including phosphotriesters, will be studied.